Email updates

Keep up to date with the latest news and content from Arthritis Research & Therapy and BioMed Central.

Open Access Research article

Adalimumab regulates intracellular TNFα production in patients with rheumatoid arthritis

Carlos Zamora-Atenza1, Cesar Diaz-Torne2, Carme Geli2, Cesar Diaz-Lopez2, M Angels Ortiz1, Patricia Moya2, Ivan Castellví2, Juan C Nieto1, Elisabet Cantó1, Jordi Casademont2, Candido Juarez3, Josep M Llobet2 and Silvia Vidal1*

Author Affiliations

1 Department of Immunology, Biomedical Research Institut Sant Pau (IBB Sant Pau), C. Antoni M. Claret, 167, 08025 Barcelona, Spain

2 Unit of Rheumatology, Department of Internal Medicine, Hospital de la Santa Creu i Sant Pau, C. Antoni M. Claret, 167, 08025 Barcelona, Spain

3 Department of Immunology, Hospital de la Santa Creu i Sant Pau, C. Antoni M. Claret, 167, 08025 Barcelona, Spain

For all author emails, please log on.

Arthritis Research & Therapy 2014, 16:R153  doi:10.1186/ar4615

Published: 18 July 2014

Abstract

Introduction

Adalimumab is a fully human anti–tumor necrosis factor α (anti-TNFα) monoclonal antibody that specifically blocks the interaction of TNFα with its receptors. It binds both soluble and transmembrane TNFα. We hypothesized that blocking these TNFα signals regulates the altered TNFα production in rheumatoid arthritis (RA) patients.

Methods

We compared, by flow cytometry, Toll-like receptor induction levels of membrane and intracellular TNFα in monocytes (iTNFα + CD14+ cells) from 12 patients before and after adalimumab treatment with those from 5 healthy donors.

Results

Before starting the treatment, the percentage of iTNFα+ CD14+ cells in the RA patients was significantly lower than that in healthy donors (mean ± SEM = 33.16 ± 4.82% vs 66.51 ± 2.4%, P < 0.001). When we added in vitro TNFα to healthy donor culture cells, levels of iTNFα+ CD14+ cells decreased, suggesting that the TNFα signal was responsible for the iTNFα+ CD14+ cell downregulation observed in the RA patients. After 2, 6 and 12 adalimumab injections, we observed significant blocking of membrane and soluble TNFα and a progressive increase in iTNFα+ CD14+ cells in ten patients with a good to moderate response as defined by the European League Against Rheumatism (EULAR) criteria. Levels of iTNFα+ CD14+ cells after 12 injections in these 10 patients were comparable to levels in healthy donors. In two patients, iTNFα+ CD14+ cell upregulation was not observed, and their EULAR-defined responses had not improved. The first patient developed antiadalimumab antibodies, explaining why adalimumab was not able to block membrane and soluble TNFα. In the second patient, adalimumab was discontinued because of adverse effects, which led to a decrease in iTNFα+ CD14+ cells to levels measured before treatment.

Conclusions

Our findings suggest that adalimumab treatment in RA patients can return iTNFα levels to those of healthy donors. This effect was not observed in the presence of neutralizing antiadalimumab antibodies.